THIORIDAZINE DOSE-RELATED EFFECTS ON BIOMECHANICAL FORCE PLATFORM MEASURES OF SWAY IN YOUNG AND OLD MEN

OBJECTIVE: Thioridazine (TDZ) is associated with an increased risk of falls. The purpose of this study was to determine whether (1) thiorida zine increases Biomechanics Force Platform (BFP) measures of sway in a dose-related manner, (2) there is a difference in sway between young and old men, (3) there is a correlation between sway and orthostatic c hanges in BP and HR. DESIGN: Seven younger (aged 20-42) and five older (aged 70-76) healthy male volunteers received, in a randomized order double-blind design, a single oral dose of 0, 25, and 50 mg of TDZ on three separate days at least 7 days apart and 75 mg on the fourth day of the study. Sway and blood pressure were measured for 24 hours. SETT ING: A general clinical research center. MEASUREMENTS: Biomechanics fo rce platform measures of postural sway were measured as the movement o f the center of pressure. The elliptical area (EA) and average velocit y (AV) were calculated with eyes open and eyes closed. Blood pressure and heart rate were measured for 5 minutes supine and 5 minutes standi ng.RESULTS: Thioridazine increases BFP sway in a dose-dependent manner . EA increased from 0.56 (SD =.51) cm(2) for placebo to 0.88 (SD = 1.0 9) cm(2) for 75 mg TDZ. AV increased from 1.07 (SD =.27) cm/sec, place bo, to 1.43 (SD =.55) cm/sec, 75 mg TDZ. Older men swayed more than yo unger men. Changes followed the expected time course for TDZ. EA and A V were associated with HR and BP, e.g., SEP versus In(EA) and In(AV) ( r = -0.21 and r = -0.22, respectively; P<.0001). CONCLUSIONS: Thiorida zine increases validated measures of fall risk dose dependently in you ng and old men. This may explain the effects of neuroleptic drugs on f all risk in older people.